Varicella is the major communicable disease of childhood for which no vaccine is available. After an attack of varicella, the virus (VZV) remains latent in the body, and then may reactivate and cause herpes zoster. Since the virus was isolated by us in 1953 progress has been slow because of the unique characteristics of the agent; the virus is cell-associated in vitro and the problem of low yields of virus hampers research; no animal model exists; the mechanisms of viral persistence are unknown; other members of the herpes-virus group exhibit transforming potential - it is not known if VZV shares this characteristic. This proposal attacks these problems. Improved yields of VZV in vitro will be sought by use of genetically defective defined human cells lines that might inhibit cytoplasmic degradation of assembled virus, and by manipulation of cultural conditions using new cell lines. The search for an animal model will focus on the guinea pig and the mouse. VZV will grow in vitro in guinea pig cells; introduction of virus will be attempted by inoculation of infected guinea pig cells via an immunologically privileged site, the anterior chamber of the eye, or by use of immunosuppressed animals. Attempts to adapt virus to the mouse will include attempts to infect mouse-human hybrid cells in vitro, and their transfer to the nude mouse. Virus persistence can be achieved in vitro by use of inhibitors such as phosphonoacetic acid, or by temperature manipulation of the virus in certain cells; using these systems mechanisms of persistence at the cellular level will be examined and the transforming potential of VZV explored.